Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

By P. Rodriguez, M. Ernstoff, Claudia P. Hernández, M. Atkins, J. Zabaleta, Rosa A. Sierra, Augusto Ochoa. Cancer Research, 2009

789 citations recorded by the source corpus.

Myeloid-derived suppressor cells (MDSC) producing arginase I are increased in the peripheral blood of patients with renal cell carcinoma (RCC). MDSC inhibit T-cell function by reducing the availability of l-arginine and are therefore considered an important tumor escape mechanism. We aimed to determine the origin of arginase I–producing MDSC in RCC patients and to identify the mechanisms used to deplete extracellular l-arginine. The results show that human MDSC are a subpopulation of activated polymorphonuclear (PMN) cells expressing high levels of CD66b, CD11b, and VEGFR1 and low levels of CD62L and CD16. In contrast to murine MDSC, human MDSC do not deplete l-arginine by increasing its uptake but instead release arginase I into the circulation. Activation of normal PMN induces phenotypic and functional changes similar to MDSC and also promotes the release of arginase I from intracellular granules. Interestingly, although activation of normal PMN usually ends with apoptosis, MDSC showed no increase in apoptosis compared with autologous PMN or PMN obtained from normal controls. High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I. These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/3d22964ea163c7404c74202e82e70b0c1489c87f

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Citations in the corpus

Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function (2010, background): “CD62L, CD16, and vascular endothelial growth factor (VEGF) receptor 1 [10].”
Myeloid-derived suppressor cell heterogeneity and subset definition. (2010, background): “Subsequently the same group defined more precisely that MDSCs in renal cancer patients belonged to a subset of activated granulocytes, expressing CD66b and VEGFR1, able to degranulate and thus release ARG1 into plasma [35].”
The Tumor Microenvironment Innately Modulates Cancer Progression (2019, background): “Other than being hypodense, MDSCs are divergent from neutrophils in several ways, including reduced expressionofCD16andCD62L, and increased expressionofArg1, CD66B, and CD11b (39, 40).”
Myeloid-derived Suppressor Cells Inhibit T Cell Activation by Depleting Cystine and Cysteine (2009, neutral): “liquid chromatography (HPLC) as described (29).”